Scientists watch live brain cell circuits spark and fire

NIH-funded scientists show new genetically engineered proteins may be important tool for the President’s BRAIN Initiative

The Electric Fly Brain Comes Alive

Scientists used a new protein, called ArcLight, to watch nerve cell electricity in a live fly brain. Courtesy of Nitabach Lab, Yale School of Medicine, New Haven, CT

Normal Fly Brain Firing

In this movie scientists simultaneously watched ArcLight glow and recorded the electricity of a brain cell with an electrode. The red and green traces at the bottom show that ArcLight glowed in parallel with changes in the cell’s electricity (white trace).

Mutant Fly Brain Firing

In this movie scientist watched mutant fly brain cells fire. The cells were genetically engineered to be over active.

What:

Scientists used fruit flies to show for the first time that a new class of genetically engineered proteins can be used to watch electrical activity in individual brain cells in live brains. The results, published in Cell, suggest these proteins may be a promising new tool for mapping brain cell activity in multiple animals and for studying how neurological disorders disrupt normal nerve cell signaling. Understanding brain cell activity is a high priority of the President’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.

Brain cells use electricity to control thoughts, movements and senses. Ever since the late eigteenth century, when Dr. Luigi Galvani induced frog legs to move with electric shocks, scientists have been trying to watch nerve cell electricity to understand how it is involved in these actions. Usually they directly mo nitor electricity with cumbersome electrodes or toxic voltage-sensitive dyes, or indirectly with calcium detectors. This study, led by Michael Nitabach, Ph.D., J.D., and Vincent Pieribone, Ph.D., at the Yale School of Medicine, New Haven, CT, shows that a class of proteins, called genetically encoded fluorescent voltage indicators (GEVIs), may allow researchers to watch nerve cell electricity in a live animal.

Dr. Pieribone and his colleagues helped develop ArcLight, the protein used in this study. ArcLight fluoresces, or glows, as a nerve cell’s voltage changes and enables researchers to watch, in real time, the cell’s electrical activity (see previous story). In this study, Dr. Nitabach and his colleagues engineered fruit flies to express ArcLight in brain cells that control the fly’s sleeping cycle or sense of smell. Initial experiments in which the researchers simultaneously watched brain cell electricity with a microscope and recorded voltage with electrodes showed that ArcLight can accurately monitor electricity in a living brain (see video). Further experiments showed that ArcLight illuminated electricity in parts of the brain that were previously inaccessible using other techniques. Finally, ArcLight allowed the researchers to watch brain cells spark and fire while the flies were awakening and smelling. These results suggest that in the future neuroscientists may be able to use ArcLight and similar GEVIs in a variety of ways to map brain cell circuit activity during normal and disease states.

This study was supported by grants from NINDS (NS055035, NS056443, NS083875, NS057631, NS083875) and NIGMS (GM098931).

GEVIs and other sensors are being developed by a group of NINDS-funded researchers who are part of the Fluorogenetic Voltage Sensors Consortium. The consortium was partly funded with grants from the American Recovery and Reinvestment Act.

NINDS (http://www.ninds.nih.gov) is the nation’s leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease – a burden borne by every age group, by every segment of society, by people all over the world.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.